Our long-term goal is to develop a therapeutic uricase that can be used in hyperuricemia and the various manifestations of gout, including gouty arthritis (acute and chronic) tophi and urate deposits in tissues and organs, and uric acid nephropathy. It is expected that the therapeutic uricase will be able to remove completely urate deposits in the body. It will also control hyperuricemia if given at intervals in small amounts. Therapeutic uricase should be able to dissolve urate deposits in a matter of hours or days, and should provide immediate relief for acute gouty arthritis attacks, with no likelihood of recurrence. Cancer patients undergoing aggressive radiation or chemotherapy against large tumor masses will be protected from excessive urate production. The specific aims of this project are to modify by covalent attachment of monomethoxypolyethylene glycol (PEG) a selected uricase with high activity, good stability, and controlled immunogenicity. Procedures for developing a homogeneous PEG-uricase are well along. Animal toxicology studies will be done in mice, rats and dogs in preparation for submission for an Investigational New Drug Number and permission to begin human clinical testing for pharmacokinetics and toxicology.